Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

CiteULike is a free service for managing and discovering scholarly references - click here to get started.

Sign In to gain access to subscriptions and/or personal tools.
The British Journal of Diabetes & Vascular Disease
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Campbell, I. W
Right arrow Search for Related Content
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

The role of metformin and pioglitazone in early combination treatment of type 2 diabetes mellitus

Ian W Campbell

Victoria Hospital, Kirkcaldy, Fife, KY2 5AH, Scotland, jackie.wallace{at}faht.scot.nhs.uk

Metformin will celebrate 50 years of clinical use in 2007. Pioglitazone was introduced into clinical practice in 1999. Both metformin and pioglitazone have positive effects on components of the metabolic syndrome, namely: insulin resistance, hyperinsulinaemia, visceral obesity, hyperglycaemia, dyslipidaemia and hypertension and risk factors involved in endothelial dysfunction, inflammation and atherosclerosis. Improvements in cardiovascular outcomes have been demonstrated in patients at high risk of macrovascular events with pioglitazone (PROactive) and in overweight patients with metformin (UKPDS 34). Pioglitazone may also help to sustain beta-cell function. Introduction of combination therapy using two differently acting oral antidiabetic agents at the time of diagnosis or early thereafter is becoming increasingly common in order to reach glycaemic targets (e.g. HbA1C ≤7.0%). The combination of metformin and pioglitazone in an early stage of type 2 diabetes enables greater likelihood that these targets can be with insulin secretagogues. attained without the risk of hypoglycaemia associated with insulin secretagogues

Key Words: metformin • pioglitazone • insulin resistance • cardiovascular risk • beta-cell preservation.

References

  • Kahn SE The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 2003; 46:3-19.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Campbell IW Pioglitazone - an oral antidiabetic agent and metabolic syndrome modulator. Can theory translate into practice? Br J Diabetes Vasc Dis 2005;5:209-16.
  • Klein R. Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care 1995;18:258-68.[Abstract]
  • Stratton IM, Adler AI, Neil HA et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405-12.[Abstract/Free Full Text]
  • Goodarzi MO, Bryer-Ash M. Metformin revisited: re-evaluation of its properties and role in the pharmacopoeia of modern antidiabetic agents. Diabetes Obes Metab 2005;7:654-65.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854-65.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Avandia Summary of Product Characteristics. 2005. 8. ACTOS Summary of Product Characteristics. 2005.
  • Bailey CJ, Feher MD Therapies for diabetes including oral agents and insulins. Birmingham: Sherborne Gibbs Limited, 2004.
  • Natali A., Ferrannini E. Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: a systematic review. Diabetologia 2006;49: 434-41.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Bailey CJ Biguanides and NIDDM. Diabetes Care 1992;15:755-72.[Abstract]
  • Cusi K., DeFronzo RA Metformin: a review of its metabolic effects. Diabetes Rev 1998;6:89-131.
  • Bailey CJ, Day C. Thiazolidinediones today. Br J Diabetes Vasc Dis 2001;1: 7-13.[Abstract/Free Full Text]
  • Diamant M., Heine R. Thiazolidinediones in type 2 diabetes mellitus: current clinical evidence. Drugs 2003;63:1373-405.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Lebovitz HE, Banerji MA Insulin resistance and its treatment with thiazolidinediones. Rec Prog Horm Res 2001;58:265-94.
  • Tan MH, Baksi A., Krahulec B. et al. Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes. Diabetes Care 2005;28:544-50.[Abstract/Free Full Text]
  • Charbonnel B., Schernthaner G., Brunetti P. et al. Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes. Diabetologia 2005;48:1093-104.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ovalle F., Bell DS Clinical evidence of thiazolidinedione-induced improvement of pancreatic beta-cell function in patients with type 2 diabetes mellitus. Diabetes Obes Metab 2002;4:56-9.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-53.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Barnett AH, O'Gara G. Diabetes and the heart. London: Churchill Livingstone, 2003.
  • Haffner SM The importance of hyperglycemia in the nonfasting state to the development of cardiovascular disease. Endocr Rev 1998;19:583-92.[Abstract/Free Full Text]
  • National Institute for Health and Clinical Excellence. Management of Type 2 diabetes: Management of blood pressure and blood lipids (Guideline H). 2002. Inherited Clinical Guideline H.
  • Reaven GM Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595-607.[Abstract]
  • Howlett HCS, Bailey CJ A risk-benefit assessment of metformin in type 2 diabetes mellitus. Drug Saf 1999;20:489-503.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Kawamori R., Matsuhisa M., Kinoshita J. et al. Pioglitazone enhances splanchnic glucose uptake as well as peripheral glucose uptake in non-insulin-dependent diabetes mellitus. AD-4833 Clamp-OGL Study Group. Diabetes Res Clin Pract 1998;41:35-43.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Herz M., Johns D., Reviriego J. et al. A randomized, double-blind, placebocontrolled, clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medication-naive patients with type 2 diabetes mellitus. Clin Ther 2003;25:1074-95.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Rosenblatt S., Miskin B., Glazer NB, Prince MJ, Robertson KE The impact of pioglitazone on glycemic control and atherogenic dyslipidemia in patients with type 2 diabetes mellitus. Coron Artery Dis 2001;12:413-23.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Bays H., Mandarino L., DeFronzo RA Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab 2004;89:463-78.[Free Full Text]
  • Bailey CJ Treating insulin resistance in type 2 diabetes with metformin and thiazolidinediones. Diabetes Obes Metab 2005;7:675-91.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Mayerson AB, Hundal RS, Dufour S. et al. The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes 2002;51:797-802.[Abstract/Free Full Text]
  • Miyazaki Y., Mahankali A., Matsuda M. et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 2002;87:2784-91.[Abstract/Free Full Text]
  • Campbell IW, Howlett HC Worldwide experience of metformin as an effective glucose-lowering agent: a meta-analysis. Diabetes Metab Rev 1995;11(suppl 1):S57-S62.[Web of Science][Medline] [Order article via Infotrieve]
  • Betteridge DJ Diabetic dyslipidaemia: past, present and future. Pract Diab Int 2004;21:78-85.[CrossRef]
  • Wild S., Byrne CD The role of treatment to increase HDL-cholesterol and decrease triglyceride concentrations in prevention of coronary heart disease in Type 2 diabetes. Diabet Med 2004;21(suppl 4):8-11.
  • Ginsberg HN Hypertriglyceridemia: new insights and new approaches to pharmacologic therapy. Am J Cardiol 2001;87:1180.
  • Chiquette E., Ramirez G., Defronzo R. A meta-analysis comparing the effect of thiazolidinediones on cardiovascular risk factors. Arch Intern Med 2004;164:2097-104.[Abstract/Free Full Text]
  • van Wijk JP, de Koning EJ, Martens EP, Rabelink TJ Thiazolidinediones and blood lipids in type 2 diabetes. Arterioscler Thromb Vasc Biol 2003;23:1744-9.[Abstract/Free Full Text]
  • Goldberg RB, Kendall DM, Deeg MA et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care 2005;28:1547-54.[Abstract/Free Full Text]
  • Derosa G., Gaddi AV, Piccinni MN et al. Differential effect of glimepiride and rosiglitazone on metabolic control of type 2 diabetic patients treated with metformin: a randomized, double-blind, clinical trial. Diabetes Obes Metab 2006;8:197-205.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Berhanu P., Kipnes MS, Khan MA et al. Effects of pioglitazone on lipid and lipoprotein profiles in patients with type 2 diabetes and dyslipidaemia after treatment conversion from rosiglitazone while continuing stable statin therapy. Diabetes Vasc Dis Res 2006;3:39-44.[CrossRef]
  • Dormandy JA, Charbonnel B., Eckland DJ et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005;366:1279-89.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ginsberg H., Plutzky J., Sobel BE A review of metabolic and cardiovascular effects of oral antidiabetic agents: Beyond glucose lowering. J Cardiovasc Risk 1999;6:337-46.[Web of Science][Medline] [Order article via Infotrieve]
  • Goke B., on behalf of the German Pioglitazone Study Group. Improved glycemic control and lipid profile in a randomized study of pioglitazone compared with acarbose in patients with type 2 diabetes mellitus. Treat Endocrinol 2002;1:329-36.[CrossRef][Medline] [Order article via Infotrieve]
  • Pavo I., Jermendy G., Varkonyi TT et al. Effect of pioglitazone compared with metformin on glycemic control and indicators of insulin sensitivity in recently diagnosed patients with type 2 diabetes. J Clin Endocrinol Metab 2003;88:1637-45.[Abstract/Free Full Text]
  • Yki-Jarvinen H. The PROactive study: some answers, many questions. Lancet 2005;366:1241-2.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Waugh J., Keating GM, Plosker GL, Easthope S., Robinson DM Pioglitazone: a review of its use in type 2 diabetes mellitus. Drugs 2006; 66:85-109.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Home PD, Pocock SJ, Beck-Nielsen H. et al. Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD): study design and protocol. Diabetologia 2005;48:1726-35.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Wiernsperger NF Metformin: intrinsic vasculoprotective properties. Diabetes Technol Ther 2000;2:259-72.[CrossRef][Medline] [Order article via Infotrieve]
  • Isoda K., Young JL, Zirlik A. et al. Metformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cells. Arterioscler Thromb Vasc Biol 2006;26:611-17.[Abstract/Free Full Text]
  • Trost S., Pratley R., Sobel B. Impaired fibrinolysis and risk for cardiovascular disease in the metabolic syndrome and type 2 diabetes. Curr Diab Rep 2006;6:47-54.[Medline] [Order article via Infotrieve]
  • Pfutzner A., Marx N., Lubben G. et al. Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control: results from the pioneer study. J Am Coll Cardiol 2005;45:1925-31.[Abstract/Free Full Text]
  • Szapary PO, Bloedon LT, Samaha FF et al. Effects of pioglitazone on lipoproteins, inflammatory markers, and adipokines in nondiabetic patients with metabolic syndrome. Arterioscler Thromb Vasc Biol 2006; 26:182-8.[Abstract/Free Full Text]
  • Shimizu H., Oh-I S., Tsuchiya T., Ohtani KI, Okada S., Mori M. Pioglitazone increases circulating adiponectin levels and subsequently reduces TNFalpha levels in Type 2 diabetic patients: a randomized study. Diabet Med 2006;23:253-7.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Bakris G., Viberti G., Weston WM, Heise M., Porter LE, Freed MI Rosiglitazone reduces urinary albumin excretion in type II diabetes. J Hum Hypertens 2003;17:7-12.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Yanagawa T., Araki A., Sasamoto K., Shirabe S., Yamanouchi T. Effect of antidiabetic medications on microalbuminuria in patients with type 2 diabetes. Metabolism 2004;53:353-7.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group. Diabet Med 1998;15:297-303.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Buchanan TA, Xiang AH, Peters RK et al. Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk hispanic women. Diabetes 2002; 51:2796-803.[Abstract/Free Full Text]
  • Xiang AH, Peters RK, Kjos SL et al. Effect of Pioglitazone on Pancreatic {beta}-Cell Function and Diabetes Risk in Hispanic Women With Prior Gestational Diabetes. Diabetes 2006;55:517-22.[Abstract/Free Full Text]
  • Leiter LA Beta-cell preservation: a potential role for thiazolidinediones to improve clinical care in Type 2 diabetes. Diabet Med 2005;22:963-72.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Walter H., Lubben G. Potential role of oral thiazolidinedione therapy in preserving beta-cell function in type 2 diabetes mellitus. Drugs 2005;65: 1-13.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Gerstein HC, Yusuf S., Holman R., Bosch J., Pogue J. Rationale, design and recruitment characteristics of a large, simple international trial of diabetes prevention: the DREAM trial. Diabetologia 2004;47:1519-27.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

The British Journal of Diabetes & Vascular Disease, Vol. 6, No. 5, 207-215 (2006)
DOI: 10.1177/14746514060060050101
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Campbell, I. W
Right arrow Search for Related Content
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?